Trichomonas vaginalis is a frequently encountered sexually transmitted parasite with worldwide distribution. The parasite is a major emerging concern in the amplification of HIV transmission, and may also be involved in increased susceptibility to cervical cancer. The disease is presently treated with metronidazole which has a 10% failure rate. In addition, due to mutagenic concerns, metronidazole is not prescribed during early pregnancy. Therefore a need for safe alternative therapy for this disease exists. The object of this proposal is to examine 1,2- naphthoquinone analogs as potential trichomonacides. Our initial findings show that several 1,2-naphthoquinone derivatives are extremely effective growth inhibitors of T. vaginalis. One of these was found to be better than 100-fold more active toward a metronidazole-refractive isolate CDC-085. SL-11051 was also found to be active at 100 mg/kg in a mouse subcutaneous assay. We propose to extend our initial findings by synthesizing new naphthoquinone analogs, some of them with short peptide sequences, such as arginine or methionine, which the parasite has a high demand for. These compounds will be tested for antitrichomonad activity in our in vitro growth assay, and those showing high activity (<0.02 mM) will be tested in vivo using the mouse subcutaneous and rate intravaginal model systems. PROPOSED COMMERCIAL APPLICATIONS: 1,2-Naphthoquinone derivatives have shown to be effective both in vitro and in vivo against T.vaginalis. This parasite causes the most prevalent non-viral, sexually transmitted disease in females. The only drug available for this disease since 1955 is F1agyl(R), and it created resistance. New effective and safe drugs are needed as alternatives.